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Nanoparticles in 472 Human Cerebrospinal Fluid: Changes in Extracellular Vesicle Concentration and miR-21 Expression
Kyue-Yim Lee1, Ji Hye Im1, Weiwei Lin2
1Department of Cancer Control, National Cancer Center Graduate School of Cancer Science and Policy, Goyang 10408, Korea.
Abstract:
Leptomeningeal metastasis (LM) has a poor prognosis and is difficult to diagnose and predict the response of treatment. In this study, we suggested that the monitoring of changes in the concentration of extracellular vesicles in cerebrospinal fluid could help diagnose or predict outcomes for LM. We measured nanoparticles in 472 human cerebrospinal fluid (CSF) from patients including LM with both Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA) after two-step centrifugations. NTA revealed that the concentration of CSF nanoparticles was significantly increased in LM compared to other groups (2.80 × 108 /mL vs. 1.49 × 108 /mL, p < 0.01). Changes in NTA-measured nanoparticles concentration after intra-CSF chemotherapy were further examined in 33 non-small cell lung cancer patients with LM. Overall survival was longer for patients with increased EV than the others (442 vs. 165 days, p < 0.001). Markers of extracellular vesicles (CD9/CD63/CD81) significantly decreased in the EV-decreased group. MicroRNA-21 expression decreased in this favorable prognostic group, whereas it increased in the EV-decreased group. In conclusion, the elevated concentration of extracellular vesicles in cerebrospinal fluid in patients with LM may be a predictive marker for survival duration. Moreover, EV changes combined with microRNA-21 might be a biomarker for monitoring the efficacy of intracranial chemotherapy of LM in non-small cell lung cancer patients.
Insights
Monitoring extracellular vesicles (EVs) in cerebrospinal fluid (CSF) can help diagnose leptomeningeal metastasis (LM). Increased EV concentration in CSF correlates with longer survival and treatment response in LM patients.
Area of Science:
- Neuro-oncology
- Biomarker Discovery
- Cerebrospinal Fluid Analysis
Background:
- Leptomeningeal metastasis (LM) presents a poor prognosis and diagnostic challenges.
- Predicting treatment response in LM is difficult.
- Extracellular vesicles (EVs) in cerebrospinal fluid (CSF) are potential diagnostic and prognostic indicators.
Purpose of the Study:
- To investigate the diagnostic and prognostic value of extracellular vesicles (EVs) in cerebrospinal fluid (CSF) for leptomeningeal metastasis (LM).
- To explore the correlation between EV concentration, patient survival, and treatment response in LM.
Main Methods:
- Analysis of nanoparticles in 472 human CSF samples using Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA).
- Examination of EV concentration changes after intra-CSF chemotherapy in 33 non-small cell lung cancer patients with LM.
- Assessment of EV markers (CD9/CD63/CD81) and microRNA-21 expression.
Main Results:
- CSF nanoparticle concentration was significantly higher in LM patients compared to controls (2.80 × 10^8 /mL vs. 1.49 × 10^8 /mL, p < 0.01).
- Patients with increased EV concentration showed longer overall survival (442 vs. 165 days, p < 0.001).
- EV marker expression and microRNA-21 levels varied between favorable and unfavorable prognostic groups.
Conclusions:
- Elevated CSF extracellular vesicle concentration may serve as a predictive marker for survival duration in LM.
- Combined analysis of EVs and microRNA-21 could monitor intracranial chemotherapy efficacy in LM, particularly in non-small cell lung cancer.
